Category Archives: surgical glue

Product Development in Surgical Glues

Surgical closure and securement products range from simple suture products to sophisticated biomaterial aids for hemostasis, sealant activity, and for adhesion prevention. Within the hemostasis field, products have the objective of rapidly achieving hemostasis and acting to seal in the presence of high pressure blood flow or air flow.

Screen Shot 2014-04-23 at 3.49.13 PMDevelopment Timelines
Natural hemostats such as gelatin, collagen and thrombin were first developed as hemostatic agents, followed by mixes and fibrin sealants. More recently, companies have introduced synthetic sealants and hemostats that accelerate the process of blood clotting and provide a stronger seal that will withstand greater pressures. These products employ various synthetic polymer chemistry systems. Glues are required to secure tissue firmly under substantial forces. In extreme cases such as musculoskeletal repair, these glues need to withstand high tension and pressure forces. Fibrin and other sealants are not strong enough for these applications and have been used as adjuncts to sutures and staples. Cyanoacrylate glues have sufficient strength for most procedures but are not yet cleared for use in the majority of internal applications due to toxicity concerns. They also lack sufficient flexibility for use in many procedures.

Efforts are progressing to develop new biomaterials capable of gluing tissues with high strength, low toxicity, and sufficient flexibility to avoid breakage of the bond. In addition, cyanoacrylate manufacturers are examining the possibility of improving cyanoacrylate technology to overcome the existing challenges of toxicity and brittleness. Despite this huge challenge, one or both of these two approaches are likely to establish new products in the next decade. In addition, the evidence of research work suggests it should be possible to create a glue technology that incorporates hemostatic properties to further enhance the role of this technology.

Apart from fibrin-based sealants and cyanoacrylate-based high-strength glues, there are three other main categories of closure/attachment products in use or in development at present.

Collagen and Thrombin Combination
Screen Shot 2014-04-23 at 3.54.26 PMCollagen is a major protein found in most mammals; the form of collagen that is generally used for wound sealant and closure is a white water-soluble fiber containing several key amino acids. In most sealants, collagen forms a matrix on which thrombin (but also fibrin, polyethylene glycol (PEG) polymers, or other compounds) are attached. The role of the collagen matrix is to channel blood with its various clotting proteins to the compounds attached to the matrix (thrombin, etc.), triggering a clotting cascade.

Polyethylene Glycol Polymer (PEG)
Screen Shot 2014-04-23 at 3.55.52 PMPolymers such as polyethylene glycol polymer (PEG) can absorb fluids and are the basis for products to seal and join tissues. CoSeal (Angiotech Pharmaceuticals, marketed by Baxter BioSurgery) and FocalSeal (Genzyme) are two products of this type. They are completely synthetic and offer quick sealing of the wound with the flexibility to expand and contract. Because these sealants are synthetic, they do not pose the risk of viral infection spreading from one person to another.

Albumin Cross-Linked with Glutaraldehyde
Screen Shot 2014-04-23 at 3.58.05 PMAlbumin, the protein that forms egg white, is one of the strongest natural adhesives in the market. Albumins are water-soluble and will coagulate when heated or combined with certain acids. When combined with glutaraldehyde, albumin forms a strong adhesive for internal surgery. The albumin/glutaraldehyde compound forms a cross-link with the tissues to be bonded that can even be stronger than the underlying tissues. In fact, the compound has been shown to withstand pressures of 500 mm–800 mm of mercury, which is more than four times normal human blood pressure.

CryoLife’s BioGlue is a widely used albumin/glutaraldehyde glue. It begins to set within 20–30 seconds of application and reaches its ultimate bonding strength within two minutes.

It is unlikely that any one formulation of tissue glue will be adequate for all applications. For example, fixing fragments of bone after significant bone trauma is likely to require an adhesive with a different modulus and strength to that required for adherence of pericardium during cardiovascular surgery. It is also likely that the sealant and hemostatic properties of these two products will need to be different. For example, to stick pericardial tissues together, the surgeon will be concerned with avoiding surgical adhesions and excessive fibrosis that might lead to problems during revision surgery. In the example of bone repair, rapid rehabilitation and avoidance of non-unions during fracture healing is a major challenge: this would suggest looking for a glue that encourages osteoblast activity and does not form an impenetrable barrier for cellular in- growth, but which can also tolerate the static and dynamic forces put upon bone.

Recently, new technologies have appeared on the market to address the need for adhesion prevention. These products have been formulated to be approvable by the FDA through device regulation routes; thus, in addition to providing a physical barrier, these products also may have some subsidiary active mechanism to achieve their objective.

Delivery Systems

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Source: CryoLife

In parallel with new products, in several instances new delivery systems have had to be developed. Surgeons also experiment with these products in an effort to produce superior results. A surgeon may, for example, mix a sealant with a few ml of saline to gain greater control over product application. Development of these delivery systems may be driven by several factors, such as: to improve the speed and ease of surgical procedures; to facilitate complex procedures that would otherwise be less successful; to better access a particular tissue; or to avoid premature mixing of two components, thus providing better control of the gluing process. New delivery systems have evolved to spray liquid hemostat solutions such as thrombin onto surgical sites to improve speed of hemostasis. Fibrin sealant is supplied as two powders that need to be solubilized and then mixed immediately prior to application to the surgical site. This has led to the development of a number of sophisticated medical delivery devices, and companies like Baxter aredeveloping single component systems that are already solubilized for immediate use in the surgical theater.

Cyanoacrylate adhesive for surgical closure is a topical-only treatment that eventually sloughs off the top surface of the wound. The product is applied to the surface of the skin to form a glue film that secures apposition of the cut edges of the incision. Currently, the cyanoacrylate is supplied in a device that aids the curing of the adhesive and ensures its safe handling and application.

Several fairly sophisticated delivery systems for new sealant and glue products have been developed or are currently under development. As new procedures are developed for cyanoacrylate and new glues, new devices will be required to aid the procedure. The devices will contribute an increasing proportion of the value associated with the gluing process.

Sophisticated surgical instruments are being developed to facilitate the application in each new indication for new high-strength glue products. High-strength glues are increasingly being utilized to repair vascular joints in coronary bypass operations. Customized instrumentation is designed to hold vessels in place and facilitate the application of exact amounts of adhesive and to avoid subsequent delays from leakage, or imperfect integration of the grafted tissues.


Source: MedMarket Diligence, LLC; Report #S190, “Worldwide Surgical Sealants, Glues, Wound Closure and Anti-Adhesion Markets, 2010-2017.”

Use of Surgical Sealants for Cranial and Spinal Dura

Surgical sealants have an enormous range of applications in the treatment of acute and chronic wounds, but while the majority of sealant revenues derives from their use in the hemostasis, closure and sealant of tissues to prevent blood loss…

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Source: MedMarket Diligence, LLC; Report #S190

… a different niche use of sealants is stopping cerebrospinal fluid leaks and other dural wound treatments associated with cranial and spinal procedures. These include their use in:

  • Cranial and spinal dural plastic surgery to prevent CSF fistulas.
  • Dural plastic surgery in residual cavities following tumor removal.
  • Dural lacerations in hemilaminectomy operations

Of this, most of the use is currently in cranial applications, but use in spinal applications is growing considerably faster:

Screen Shot 2014-04-07 at 9.44.53 AM

Source: MedMarket Diligence, LLC; Report #S190

 

 

 

The increasing problem of chronic wounds, and their medtech solutions

Wounds have many different sources, etiologies and forms and, therefore, demand a range of approaches. By virtue of these differences, they have considerably different costs. At the top of the list of wound culprits driving up cost is the category of chronic wounds. Simply put, these wounds are very slow to heal due to poor circulation at the site (e.g., decubitus stasis, or pressure, ulcers), concomitant health issues (diabetes) and the difficulty in changing the local environment toward one with conditions more conducive to the healing process.

Chronic wounds are not the most common — that is a category represented by surgical wounds, in which the wound has been created medically or surgically in order to excise or otherwise manage diseased tissue. But surgical wounds, traumatic wounds and lacerations are by their nature acute and, especially for surgical wounds, can be surgically managed to create clean wound edges, good vascularization and other conditions that accelerate healing. Therefore, while the volume of surgical and traumatic wounds and lacerations is significant, their costs are manageable and their growth is unremarkable.

But the costs of chronic wounds are higher due to both the types of different products required and the length of time required for those products to be used. Moreover, given the association of chronic wounds with conditions that are growing in prevalence due to increasing incidence of obesity, diabetes and other conditions, combined with an aging population that is increasingly sedentary, the prevalence of chronic wounds is shifting the balance among wound types. Below is the balance of wound types by prevalence worldwide in 2011, followed by the projected balance of wound types in 2025.

Worldwide Share of Wound Prevalence By Type, 2011

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Source: MedMarket Diligence, LLC; Report #S190 and Report #S249.

 

Worldwide Share of Wound Prevalence By Type, 2025

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Source: MedMarket Diligence, LLC; Report #S190 and Report #S249.

Surgical wounds offer the potential for use of devices which can ensure hemostasis, prevent internal adhesions and anastomoses, secure soft tissue, and close the skin. Traumatic wounds also offer potential for skin closure products and for hemostats, and adhesion prevention during post-trauma surgery. New wound-covering sealant products may also offer potential for treatment of cuts, grazes, and burns.

Chronic wounds are generally not amenable to treatment by adhesives, sealants and hemostats unless the wound has either been debrided to a sterile bleeding surface (in which case it becomes like a surgical wound), or the product offers some stimulant activity. Many hemostats exhibit some inflammatory and cytokinetic activity, which has been associated with accelerated healing. However, this inflammatory activity has also been known to burn the patient’s skin. Chronic wounds are instead dealt with often by a combination of debridement, frequent dressing changes, products to address local vascular circulation and pressure (negative and positive) and others. Progress is being made in reducing the associated healing times, but a large opportunity remains.

Sales of Sealants, Hemostasis, Other Closure a Large, Shifting Market Worldwide

Products that provide hemostasis, closure, sealing and anti-adhesion of wounds comprised long established products (e.g., tapes, sutures, etc.) as well as a variety of advanced products such as fibrin and other surgical sealants, surgical glues, hemostats and products to prevent post-surgical adhesion.  While traditional products are being innovated to keep pace with advanced products (for example, through the development of absorbable sutures), the shift of caseload and product sales away from traditional products appears unrelenting.

As a result, the balance of the competitive landscape is forecast to shift over the next few years toward advanced sealing, hemostasis, closure and anti-adhesion products.  Below is illustrated, in a combined “donut” chart, this shift from 2012 to 2017 in the share of the global market for these products.

sealants_donut_2012-2017

Source: MedMarket Diligence Report #S190, “Worldwide Surgical Sealants, Glues, Wound Closure and Anti-Adhesion Markets, 2012-2017.”

These percentage shifts may not seem significant unless one considers that the global market for these products is over $5 billion.

 

Potential for the Use of Hemostats, Sealants, Glues and Adhesion Prevention Products, Worldwide

The MedMarket Diligence Report #S190, “Worldwide Surgical Sealants, Glues, Wound Closure and Anti-Adhesion Markets, 2012-2017″, details the complete range of sealants & glues technologies used in traumatic, surgical and other wound closure, including tapes, sutures/staples/mechanical closure, hemostats, fibrin sealants/glues and medical adhesives and anti-adhesion products. The report details current clinical and technology developments, with data on products in development (detailing market status) and on the market; market size and forecast; competitor market shares; competitor profiles; and market opportunity. The report provides full year actual data from 2011. The report provides a worldwide forecast to 2017 of the markets for these technologies, with emphasis on the market impact of new technologies through the forecast period. The report provides specific forecasts and shares of the worldwide market by segment for Americas (detail for U.S., Rest of North America and Latin America), Europe (detail for United Kingdom, German, France, Italy, Spain, Rest of Europe), Asia/Pacific (detail for Japan, Korea, Rest of Asia/Pacific) and Rest of World. The report provides background data on the surgical, disease and traumatic wound patient populations targeted by current technologies and those under development, and the current clinical practices in the management of these patients, including the dynamics among the various clinical specialties or subspecialties vying for patient population and facilitating or limiting the growth of technologies. The report establish the current worldwide market size for major technology segments as a baseline for and projecting growth in the market through 2017. The report assesses and projects the composition of the market as technologies gain or lose relative market performance over this period. The report profiles 122 active companies in this industry, providing data on their current products, current market position and products under development.

See description, table of contents and list of exhibits at http://www.mediligence.com/rpt/rpt-s190.htm.

Wound management: A $21.8 billion+ worldwide market in 2021

The worldwide market for products in wound management, as reflected in the MedMarket Diligence report #S249, encompasses twelve discrete product segments:

  • Traditional Adhesive Dressings
  • Traditional Gauze Dressings
  • Non-Adherent Dressings
  • Film Dressings
  • Foam Dressings
  • Hydrogel Dressings
  • Hydrocolloid Dressings
  • Alginate Dressings
  • Antimicrobial Dressings
  • Negative Pressure Wound Therapy Devices
  • Bioengineered Skin and Skin Substitutes
  • Wound Care Growth Factors

These segments include traditional wound care products, like dressings and bandages, but also include their more evolved forms with embedded components or constructions to enhance wound healing by shortening healing times or improving outcomes. But, wound care has also evolved to included equipment/device-mediated care as in NPWT as well as biologically-derived or engineered products in regenerative medicine.

The MedMarket Diligence report details the current and forecast wound market by product type in North and South America, the European Union, Asia/Pacific and Rest of World, and looks at markets and growth rates by product and country for the years 2012-2021.

The world market in 2012 stood at approximately $12.45 billion. By 2021, the total wound management market represented by the segments listed above is projected to be worth over $21.85 billion million, reflecting a 2013-2021 CAGR over 7%.

wound-pie-2013

Source: Report #S249.

There are some market restraints at work, primarily the high cost of the new technologies. Not all country healthcare budgets can afford advanced wound care products, even if they are proven to decrease healing times and hospital costs over the longer run. The development of substitute products threatens existing product categories, while a lack of sufficient clinical and economic evidence backing new technology hinders growth and acceptance of some of the more advanced wound management technologies. In addition, improved wound prevention and a lack of regulation on tissue engineering in the EU are also expected to hold back the development of new technologies.

In addition to market restraints, there are a number of drivers that are expected to shape this market in the years to come. One of the primary drivers is the aging of the global population. Chronic diseases, such as circulatory conditions, anemias and autoimmune diseases influence the healing process as a result of their influence on a number of bodily functions. Illnesses that cause the most significant problems include diabetes, chronic obstructive pulmonary disease (COPD), arteriosclerosis, peripheral vascular disease (PVD), heart disease, and any conditions leading to hypotension, hypovolemia, edema, and anemia. While chronic diseases are more frequent in the elderly, wound healing will be delayed in any patient with underlying illness. Happily, most wounds heal without any problems. However, chronic wounds may take months or years to fully close, or may never close. Chronic wounds adversely affect the individual’s quality of life, and are a leading cause of burgeoning healthcare costs.

Type 2 diabetes represents 85-95% of all diabetes in developed countries, and accounts for an even higher percentage in developing countries. There were 26 million diabetic patients in the US in 2012 and 285 million patients globally.   Of these patients, approximately 15% will develop a diabetic foot ulcer and 50% of these will become infected, representing an estimated 2 million patients. Diabetic foot infections are currently treated with systemic antibiotics, but the estimated failure rate of antibiotics for diabetic foot ulcers is in excess of 22%.

A patient with diabetes is at significant risk of damage to tissues caused by impaired homeostasis due to the disease process. For example there is a tendency for such tissues to develop blockages in smaller blood vessels, which reduces the ability of these vessels to provide sufficient oxygen to tissues already under stress due to compromised nutrient supply and the diabetic condition. These patients then develop arterial ulcers. They may also have a tendency to suffer from venous ulcers, due to the underlying poor condition of cells as a result of the diabetes.

The diabetic foot is the most common cause of non-traumatic lower extremity amputations in the US and Europe: there is an average of 82,000 amputations per year in the U.S., costing an estimated $1.6 billion annually. The estimated cost of foot ulcer care in the U.S. ranges from $4,595 per ulcer episode to more than $28,000 and the total annual cost of foot ulcer care in the US has been estimated to be as high as $5 billion.

Pressure, or decubitus, ulcers are another of the most common types of chronic wounds. The treatment of pressure ulcers places a major burden on healthcare systems worldwide, with an emerging additional cost of litigation increasing in importance over recent years. Healthcare practitioners need to be aware of both the direct and indirect costs and consider how the implementation of prevention protocols may offer cost savings in the longer term. The cost of a dressing for example as a prevention tool is minimal in comparison to the costs of treating an established pressure ulcer.

Following are a few hard numbers on the true financial cost of pressure ulceration:

  • The estimated cost to the US hospital sector is $11 billion per annum
  • The estimated cost to the UK national health service is estimated at £1.4-£2.1 billion annually (4% of total NHS expenditure)
  • Lawsuits remain common in both acute and long term care — with high payments in certain cases
  • The average cost to treat an individual with an unstageable ulcer or a deep tissue injury is estimated to be $43,180
  • The average length of stay in hospital is almost three times longer for chronic wounds
  • The mean hospital cost for management of pressure ulcers in the U.S. is $14,426. In comparison, the same cost in Korea is identified as $3,000-$7,000.

The cost of treating chronic wounds is one element driving the development and utilization of advanced wound care technologies. Other drivers are the aging of the population, and the obesity epidemic, which is expected to produce a wave of diabetics in the years to come.

Worldwide Wound Management Market, Segment Size & Growth, 2013-2021

wound-bubbles-2013-2021

Source: Report #S249.

In 2009, four companies (Johnson and Johnson, Kinetic Concepts Inc., Hill-Rom and Smith & Nephew) were responsible for about 60 percent of total market revenue. However, mergers, acquisitions and sales of intellectual property have rapidly changed the market share picture. By the end of 2012, more than half of the global wound care market was held by Johnson and Johnson, 3M, Smith & Nephew, and Systagenix. In addition, competition on price has driven down prices in the well established (i.e., traditional wound care) markets, while novel technologies are taking hold with introductory revenues and generating high, early stage growth rates.


For the complete analysis of the worldwide wound management market, see “Wound Management, Worldwide Market and Forecast to 2021: Established and Emerging Products, Technologies and Markets in the Americas, Europe, Asia/Pacific and Rest of World” (Report #S249).

Global market for surgical sealants, glues, hemostats and anti-adhesion

Potential for the Use of Hemostats, Sealants, Glues and Adhesion Prevention Products, Worldwide

This report details the complete range of sealants & glues technologies used in traumatic, surgical and other wound closure, including tapes, sutures/staples/mechanical closure, hemostats, fibrin sealants/glues and medical adhesives and anti-adhesion products. The report details current clinical and technology developments, with data on products in development (detailing market status) and on the market; market size and forecast; competitor market shares; competitor profiles; and market opportunity. The report provides full year actual data from 2011. The report provides a worldwide forecast to 2017 of the markets for these technologies, with emphasis on the market impact of new technologies through the forecast period. The report provides specific forecasts and shares of the worldwide market by segment for Americas (detail for U.S., Rest of North America and Latin America), Europe (detail for United Kingdom, German, France, Italy, Spain, Rest of Europe), Asia/Pacific (detail for Japan, Korea, Rest of Asia/Pacific) and Rest of World. The report provides background data on the surgical, disease and traumatic wound patient populations targeted by current technologies and those under development, and the current clinical practices in the management of these patients, including the dynamics among the various clinical specialties or subspecialties vying for patient population and facilitating or limiting the growth of technologies. The report establish the current worldwide market size for major technology segments as a baseline for and projecting growth in the market through 2017. The report assesses and projects the composition of the market as technologies gain or lose relative market performance over this period. The report profiles 122 active companies in this industry, providing data on their current products, current market position and products under development.

See description, table of contents and list of exhibits at http://www.mediligence.com/rpt/rpt-s190.htm Published February 2012..

Global and regional growth rates for wound care product sales

Manufacturers of wound care products, from traditional dressings and bandages to growth factors and bioengineered skin, see variable sales growth driven by different levels of new product adoption, variations in clinical practices, and other technology, reimbursement, regulatory, economic and other forces that vary by geography across the globe. The balance of sales across multiple wound care product types can be radically different from country to country and region to region.

Emerging from the 2013 analysis (Report #S249) by MedMarket Diligence are the current and forecast wound care product sales resulting from the net effect, region by region, of these multiple forces. Below is illustrated the high growth country/product segments in wound management, reflecting the rapid adoption of new technologies such as growth factors and bioengineered skin, as well as older products such as alginates that are gaining sales in rapidly developing economies.

wound-country-high

Source: MedMarket Diligence, LLC; Report #S249, “Wound Management, Worldwide Market and Forecast to 2021: Established and Emerging Products, Technologies and Markets in the Americas, Europe, Asia/Pacific and Rest of World.”

At the other end of the extreme are those very well established products growing at less than anemic rates in countries where the economy is not as robust and/or where the growth has been superseded by sales of more novel products. Conventional dressings and bandages offer considerably less demand than do growth factors, bioengineered skin and skin substitutes and similar new products.

wound-country-low

Source: MedMarket Diligence, LLC; Report #S249

Of course, growth of sales in wound management products (and any product) is defined as the percentage change in sales volume over time. Smaller markets (typically soon after they have formed as a result of their initial commercialization) tend to grow on a percentage basis much faster. Indeed, a $1 dollar sale in year 1 followed by a $2 sale in year 2 represents a 100% growth rate, while a $1 increase in sales from year 1 to year 2 for a $100 million market represents virtually zero growth. Conversely, a 1% increase in a $1.75 billion market is a $17.5 million increase. This is indeed obvious, but must be kept in mind when considering the growth rates discussed above.